Department of Biomedical Sciences
3302 Gaston Ave.
Dallas, Texas 75246
Education and Post-Graduate Training
Postdoctoral Fellowship, Department of Oral Biology, School of Dentistry, University of Missouri-Kansas City (2007-2008)
Ph.D., Department of Oral Biology, School of Dentistry, University of Missouri-Kansas City, Kansas, USA (2007)
Postdoctoral Fellowship, Department of Oral Biology, School of Dentistry, University of Missouri-Kansas City (1999-2002)
M.S., Department of Medical Microbiology, Qingdao Medical College, Qindao Medical College, China (1997)
M.D., Qingdao Medical College, Qingdao, China (1994)
Assistant Professor (Tenure Track), Department of Biomedical Sciences, Texas A&M University College of Dentistry (2012-present)
Assistant Professor (Research), Department of Biomedical Sciences, College of Dentistry, Texas A&M Health Science Center (2009 - 2012)
Instructor, Department of Medical Microbiology, Medical College of Qingdao University, Qingdao, China (1997-1999)
Teaching responsibilities include Physiology (dental hygiene), Oral Histology (dental and dental hygiene) and Cellular and Molecular Biology (graduate)
The long-term goal of my research is to identify effective and noninvasive therapeutic/preventive agents for clinical management of inheritable dentin disorders. The inheritable dentin disorders are caused by mutations in certain genes, such as dentin matrix protein 1 (DMP1) or dentin sialophosphoprotein (DSPP). To achieve such a goal, we not only need to understand the functions of the normal genes, but also need to know the consequences of a gene mutation. Therefore, all my current research focuses on understanding how normal genes control tooth morphogenesis, odontoblast differentiation and dentin formation, and on how a mutation changes the functions of a gene and causes the dentin defects. With these fundamental studies, I expect that one day, we can develop therapeutic agents to prevent the dentin defects from occurring in patients suffering from the inheritable dentin disorders.
Autosomal recessive hypophosphatemic rickets/osteomalacia (ARHR) associated with DMP1 mutations: DMP1 is largely known as an extracellular non-collagenous matrix protein, highly expressed in odontoblasts in tooth and in osteoblasts/osteocytes in bone. DMP1 mutations in humans result in an inheritable disease, known as autosomal recessive hypophosphatemic rickets/osteomalacia (ARHR), characterized by the dental and skeletal defects (lack of minerals) and hypophosphatemia (lack of phosphate in blood). However, the way in which the loss of DMP1 function causes these defects remains largely unknown. We propose that a nuclear isoform of DMP1 (referred to as “nuDMP1”) is translated from an alternative start codon of the same messenger RNA that encodes the secretory DMP1. We further propose that this nuDMP1 is responsible for governing the terminal differentiation of the odontoblasts and osteoblasts whereas the secretory DMP1 participates in extracellular matrix biomineralization. Successful completion of this proposed research will help elucidate the pathogeneses of hypophosphatemic rickets caused by DMP1 mutations in humans, therefore providing guidance for clinical management of hypophosphatemic rickets.
Dentinogenesis Imperfecta (DGI) and Dentin Dysplasia (DD) associated DSPP mutations: DSPP is predominantly expressed in odontoblasts in tooth. It is mainly found as two cleaved products of dentin sialoprotein (DSP) and dentin phosphoprotein (DPP) in the dentin matrix. DSPP mutations in humans may cause various inheritable autosomal dominant dentin disorders, including non-syndromic dentinogenesis imperfecta (DGI) type II and type III and dentin dysplasia (DD) type II. The non-syndromic DGI is the most commonly inherited dentin disorder that affects one in every 6,000 to 8,000 people. While significant progress has been made in understanding how normal DSPP protein regulates dentin biomineralization, it is largely unknown how various mutant DSPP proteins cause the dentin disorders. We are currently using both in vitro approaches and animal models to investigate how various DSPP mutations cause the dentin defects. These studies will have the potential to develop new, noninvasive and preventive agents for treating the DGI/DD patients associated with DSPP mutations.
Identification and Function of nuDMP1 in Odontoblast Differentiation. NIH/NIDCR R01DE023365; 2013-2017 (PI)
Studies of the Roles of Twist1 and E12 in Tooth Morphogenesis. NIH/NIDCR R03DE0217773; 2011-2014 (PI)
1) Liang T, Meng T, Wang S, Qin C, Lu Y. The LPV Motif is Essential for the Efficient Export of Secretory DMP1 from the Endoplasmic Reticulum. J Cell Physiol. 2015 Nov 23. doi: 10.1002/jcp.25265.
2) Meng T, Huang Y, Wang S, Zhang H, Dechow PC, Wang X, Qin C, Shi B, D'Souza RN, Lu Y. Twist1 Is Essential for Tooth Morphogenesis and Odontoblast Differentiation. J Biol Chem. 2015 Dec 4;290(49):29593-602. PMCID: PMC4705958
3) Liu C, Wang X, Zhang H, Xie X, Liu P, Liu Y, Jani PH, Lu Y, Chen S, Qin C. Immortalized Mouse Floxed Fam20c Dental Papillar Mesenchymal and Osteoblast Cell Lines Retain Their Primary Characteristics. J Cell Physiol. 2015 Nov;230(11):2581-7.
4) Kamel-ElSayed SA, Tiede-Lewis LM, Lu Y, Veno PA, Dallas SL. Novel approaches for two- and three-dimensional multiplexed imaging of osteocytes. Bone. 2015 Mar 17;76:129-140.
5) Huang Y, Meng T, Wang S, Zhang H, Mues G, Qin C, Feng JQ, D’Souza RN, Lu Y. Twist1- and Twist2-haploinsufficiency results in reduced bone formation. PLoS One. 2014 Jun 27;9(6):e99331. PMCID: PMC4074031
6) Lin SX, Zhang Q, Zhang H, Yan K, Ward L, Lu Y, Feng JQ. Nucleus-targeted Dmp1 transgene fails to rescue dental defects in Dmp1 null mice. Int J Oral Sci. 2014 Sep;6(3):133-41. PMCID: PMC4170153
7) Lin S, Zhang Q, Cao Z, Lu Y, Zhang H, Yan K, Liu Y, Mckee MD, Qin C, Chen Z, Feng JQ. Constitutive nuclear expression of dentin matrix protein 1 fails to rescue the Dmp1-null phenotype. J Biol Chem. 2014 Aug 1;289(31):21533-43. PMCID: PMC4118114
8) Wang X, Wang J, Yuan B, Lu Y, Feng JQ, Qin C. Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice. Connect Tissue Res. 2014 Aug;55(4):299-303. PMCID: PMC4403636
9) Gibson MP, Jani P, Wang X, Lu Y, Qin C. Overexpressing the NH2-terminal fragment of dentin sialophosphoprotein (DSPP) aggravates the periodontal defects in Dspp knockout mice. J Oral Biosci. 2014 Nov 1;56(4):143-148. PMCID: PMC4224573
10) Wang X, Jung J, Liu Y, Yuan B, Lu Y, Feng JQ, Qin C. The specific role of FAM20C in amelogenesis. Journal of Dental Research. J Dent Res. 2013 Nov; 92(11):995-9. PMCID: PMC3797537.
11) Gibson MP, Jani P, Liu Y, Wang X, Lu Y, Feng JQ, Qin C. Failure to process Dentin Sialophosphoprotein (DSPP) into fragments leads to periodontal defects in mice. European Journal of Oral Sciences. Eur J Oral Sci. 2013 Dec; 121(6):545-50. PMCID: PMC3825804.
12) Mammoto T, Jiang E, Jiang A, Lu Y, Juan AM, Chen J, Mammoto A. Twist1 Controls Lung Vascular Permeability and Endotoxin-induced Pulmonary Edema by Altering Tie2 Expression. PLoS One. 2013 Sep 2;8(9):e73407. PMCID: PMC3759405
13) Huang Y, Lu Y, Mues G, Wang S, Bonds J, D'Souza R. Functional evaluation of a novel tooth agenesis-associated bone morphogenetic protein 4 prodomain mutation. Eur J Oral Sci. 2013 Aug;121(4):313-8. PMCID: 3711029.
14) Gibson MP, Liu Q, Zhu Q, Lu Y, Jani P, Wang X, Liu Y, Paine ML, Snead ML, Feng JQ, Qin C. Role of the NH2 -terminal fragment of dentin sialophosphoprotein in dentinogenesis. Eur J Oral Sci. 2013 Apr;121(2):76-85. PMCID: 3602929.
15) Gibson MP, Zhu Q, Wang S, Liu Q, Liu Y, Wang X, Yuan B, Ruest LB, Feng JQ, D'Souza RN, Qin C, Lu Y. The rescue of dentin matrix protein 1 (DMP1)-deficient tooth defects by the transgenic expression of dentin sialophosphoprotein (DSPP) indicates that DSPP is a downstream effector molecule of DMP1 in dentinogenesis. J Biol Chem. 2013 Mar 8;288(10):7204-14.PMCID: 3591629.
16) Zhu Q, Gibson MP, Liu Q, Liu Y, Lu Y, Wang X, Feng JQ, Qin C. Proteolytic Processing of Dentin Sialophosphoprotein (DSPP) Is Essential to Dentinogenesis. J Biol Chem. 2012 Aug 31;287(36):30426-35.PMCID: PMC3436292.
17) Wang X, Wang S, Lu Y, Gibson MP, Liu Y, Yuan B, Feng JQ, Qin C. FAM20C plays an essential role in the formation of murine teeth. J Biol Chem. 2012 Oct 19;287(43):35934-42. PMCID: PMC3476261
18) Wang X, Wang S, Li C, Gao T, Liu Y, Rangiani A, Sun Y, Hao J, George A, Lu Y, Groppe J, Yuan B, Feng JQ, Qin C. Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PLoS Genet. 2012;8(5):e1002708. PMCID: PMC3355082.
19) Siyam A, Wang S, Qin C, Mues G, Stevens R, D'Souza RN, Lu Y. Nuclear localization of DMP1 proteins suggests a role in intracellular signaling. Biochem Biophys Res Commun. 2012 Aug 3;424(3):641-6. PMCID: PMC3412887.
20) Lu Y, Li Y, Cavender AC, Wang S, Mansukhani A, D'Souza RN. Molecular studies on the roles of Runx2 and Twist1 in regulating FGF signaling. Dev Dyn. 2012 Nov;241(11):1708-15. PMCID: PMC4153435.
21) Zhu Q, Prasad M, Kong H, Lu Y, Sun Y, Wang X, Yamoah A, Feng JQ, Qin C. Partial blocking of mouse DSPP processing by substitution of Gly(451)-Asp(452) bond suggests the presence of secondary cleavage site(s). Connect Tissue Res. 2012;53(4):307-12. PMCID: PMC3676176.
22) Rangiani A, Cao Z, Sun Y, Lu Y, Gao T, Yuan B, Rodgers A, Qin C, Kuro OM, Feng JQ. Protective Roles of DMP1 in High Phosphate Homeostasis. PLoS One. 2012;7(8):e42329. PMCID: PMC3411740.
23) Zhang R, Lu Y, Ye L, Yuan B, Yu S, Qin C, Xie Y, Gao T, Drezner MK, Bonewal LF, Feng JQ. Unique roles of phosphorus in endochondral bone formation and osteocyte maturation. J Bone Miner Res. 2011;26(5):1047-56. PMCID: PMC3179305.
24) Sun Y, Lu Y, Chen L, Gao T, D'Souza R, Feng JQ, Qin C. DMP1 processing is essential to dentin and jaw formation. J Dent Res. 2011;90(5):619-24. PMCID: PMC3077457.
25) Lu Y, Yuan B, Qin C, Cao Z, Xie Y, Dallas SL, McKee MD, Drezner MK, Bonewald LF, Feng JQ. The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa C-terminal fragment. J Bone Miner Res. 2011;26(2):331-40. PMCID: PMC3179348.
26) Li Y, Lu Y, Maciejewska I, Galler KM, Cavender A, D'Souza RN. TWIST1 promotes the odontoblast-like differentiation of dental stem cells. Adv Dent Res. 2011;23(3):280-4. PMCID: PMC3144037.
27) Sun Y, Lu Y, Chen S, Prasad M, Wang X, Zhu Q, Zhang J, Ball H, Feng J, Butler WT, Qin C. Key proteolytic cleavage site and full-length form of DSPP. J Dent Res. 2010;89(5):498-503. PMCID: PMC2873034.
28) Lv K, Huang H, Lu Y, Qin C, Li Z, Feng JQ. Circling behavior developed in Dmp1 null mice is due to bone defects in the vestibular apparatus. Int J Biol Sci. 2010;6(6):537-45. PMCID: PMC2945924.
29) Jiang B, Cao Z, Lu Y, Janik C, Lauziere S, Xie Y, Poliard A, Qin C, War LM, Feng JQ. DMP1 C-terminal mutant mice recapture the human ARHR tooth phenotype. J Bone Miner Res. 2010;25(10):2155-64. PMCID: PMC3153318.
30) Peng T, Huang B, Sun Y, Lu Y, Bonewald L, Chen S, Butler WT, Feng JQ, D’Souza RN, Qin C. Blocking of proteolytic processing and deletion of glycosaminoglycan side chain of mouse DMP1 by substituting critical amino acid residues. Cells Tissues Organs. 2009;189(1-4):192-7. PMCID: PMC2666981.
31) Lu Y, Qin C, Xie Y, Bonewald LF, Feng JQ. Studies of the DMP1 57-kDa functional domain both in vivo and in vitro. Cells Tissues Organs. 2009;189(1-4):175-85. PMCID: PMC2667139.
32) Huang B, Maciejewska I, Sun Y, Peng T, Qin D, Lu Y, Bonewald L, Butler WT, Feng JQ, Qin C. Identification of full-length dentin matrix protein 1 in dentin and bone. Calcif Tissue Int. 2008;82(5):401-10. PMCID: PMC2666980.
33) Lu Y, Ye L, Yu S, Zhang S, Xie Y, McKee MD, Li YC, Kong J, Eick JD, Dallas SL, Feng JQ. Rescue of odontogenesis in Dmp1-deficient mice by targeted re-expression of DMP1 reveals roles for DMP1 in early odontogenesis and dentin apposition in vivo. Dev Biol. 2007;303(1):191-201. PMCID: PMC2059935.
34) Lu Y, Xie Y, Zhang S, Dusevich V, Bonewald LF, Feng JQ. DMP1-targeted Cre expression in odontoblasts and osteocytes. J Dent Res. 2007;86(4):320-5.
35) Zhang K, Barragan-Adjemian C, Ye L, Kotha S, Dallas M, Lu Y, Zhao S, Harris M, Harris SE, Feng JQ, Bonewald LF. E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation. Mol Cell Biol. 2006;26(12):4539-52. PMCID: PMC1489126.
36) Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, Yu X, Rauch F, Davis SI, Zhang S, Rios H, Drezner MK, Quarles LD, Bonewald LF, White KE. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. 2006;38(11):1310-5. PMCID: PMC1839871.
37) Yang W, Lu Y, Kalajzic I, Guo D, Harris MA, Gluhak-Heinrich J, Kotha SE, Bonewald LF, Feng JQ, Rowe DW, Turner CH, Robling AG, Harris S. Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo. J Biol Chem. 2005;280(21):20680-90.
38) Lu Y, Zhang S, Xie Y, Pi Y, Feng JQ. Differential regulation of dentin matrix protein 1 expression during odontogenesis. Cells Tissues Organs. 2005;181(3-4):241-7.
39) Ye L, MacDougall M, Zhang S, Xie Y, Zhang J, Li Z, Lu Y, Mishina Y, Feng JQ. Deletion of dentin matrix protein-1 leads to a partial failure of maturation of predentin into dentin, hypomineralization, and expanded cavities of pulp and root canal during postnatal tooth development. J Biol Chem. 2004;279(18):19141-8.
40) Feng JQ, Huang H, Lu Y, Ye L, Xie Y, Tsutsui TW, Kunieda T, Castranio T, Scott G, Bonewald LB, Mishina Y. The Dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development. J Dent Res. 2003;82(10):776-80.
41) Zhang J, Tan X, Contag CH, Lu Y, Guo D, Harris SE, Feng JQ. Dissection of promoter control modules that direct Bmp4 expression in the epithelium-derived components of hair follicles. Biochem Biophys Res Commun. 2002;293(5):1412-9.
42) Feng JQ, Zhang J, Tan X, Lu Y, Guo D, Harris SE. Identification of cis-DNA regions controlling Bmp4 expression during tooth morphogenesis in vivo. J Dent Res. 2002;81(1):6-10.
43) Fen JQ, Zhang J, Dallas SL, Lu Y, Chen S, Tan X, Owen M, Harris SE, MacDougall M. Dentin matrix protein 1, a target molecule for Cbfa1 in bone, is a unique bone marker gene. J Bone Miner Res. 2002;17(10):1822-31.
The 9th International Conference on the Chemistry and Biology of Mineralized Tissues New Investigator Award (2007)
American Society for Bone and Mineral Research (ASBMR) 28th Annual Meeting Young Investigator Award (2006)
ASBMR-International Chinese Hard Tissue Society (ICHTS) Webster Jee Young Investigator Award (2005)